Globoid cell leukodystrophy

Alternative names

Krabbe disease; Galactosylcerebrosidase deficiency; Galactosylcereamidase deficiency

Definition

Krabbe disease is an inherited disorder characterized by a deficiency of the enzyme galactocerebroside beta-galactosidase (galactosylcereamidase). It results in destruction of myelin, a fatty material that surrounds and insulates many of the nerves.

Causes, incidence, and risk factors

Krabbe disease is inherited as an autosomal recessive trait. It is most common among people of Scandinavian descent, but it generally affects about 1 in 150,000 infants. Absence of the enzyme galactocerebroside beta-galactosidase causes increasing destruction of myelin. This results in progressive destruction of the nervous system.

Krabbe disease has an early onset form and a late onset form. In the early form, symptoms begin in the first months of life with feeding problems and failure to thrive, unexplained fevers, and vomiting.

Changes in muscle tone are frequent. Seizures may begin very early and are severe. Visual and hearing losses are progressive. Affected children eventually assume an unusual, rigid body position called decerebrate posturing. Death follows shortly thereafter, usually before the second year of life.

The late onset form of the disease begins in late childhood or early adolescence. Visual problems progressing to blindness may be the first symptom. Gait disturbance (ataxia) and muscle rigidity lead to progressive disability.

Symptoms

• Family history of Krabbe disease, especially in a sibling
  
• Infantile irritability and sensitivity to loud sounds
  
• Feeding difficulties
  
• Vomiting
  
• Failure to thrive
  
• Unexplained fevers
  
• Changing muscle tone from floppy to rigid
  
• Seizures, deterioration in function of nerves in brain and body
  
• Infant who ceases to follow faces or motion (indicates blindness)
  
• Decreased hearing that progresses to deafness
  

Signs and tests
Examination of the retina may show optic atrophy. Abnormal posturing may be evident (opisthotonos and decerebrate posturing) in late stages of the disorder. There may be signs of deafness.

Tests:

• Galactocerebroside beta-galactosidase levels (levels can be measured from the serum, white blood cells, chorionic villi, and fibroblasts)